Carcinogenic doses of 7, 12-dimethylbenz(Alpha)anthracene (DMBA) failed to induce mammary carcinomas in the rats that have received N6, O2 feet-dibutyryl cyclic adenosine 3 feet, 5 feet-monophosphate (DBcAMP). We now report that the anticarcinogenic effect of DBcAMP correlates with its effect on DNA binding of the carcinogen and on gene expression. The log phase mammary epithelia cell cultures were used to determine the effect of DBcAMP on DMBA binding to DNA. We observed that DBcAMP inhibits the covalent binding of DMBA to DNA of mammary epithelial cells of the carcinogen-susceptible 50-day-old rats but not that of the unsusceptible 35- and 110-day-old virgins. The inhibitory effect of DBcAMP was appreciable at the concentration of 10 to the -7 M, 1/10 the concentration of [3H]DMBA. DBcAMP at 10 to the -6 M concentration exhibited the maximal inhibition of DMBA binding: the binding in the 50-day-old virgin epithelial cells was reduced to the level of the bindings observed in the epithelial cells of 35- and 110-day-old virgins. The inhibitory effect of DBcAMP on DMBA binding to DNA reflected in the genomic expression. The in vitro translation products of poly(A)+ RNAs from mammary glands of young virgin rats (50-day-old) differed from those of old virgins (110-day-old). The difference was localized in four protein bands of the electrophoretic pattern that increased in their concentration and one protein band that decreased in the old virgin glands. DBcAMP administered in vivo altered the genetic transcripts of the young virgin glands to become similar to that of the old virgin glands. DMBA feeding did not appreciably alter the translation protein pattern of the young virgin glands. However, when DMBA was fed to the young virgins that had received DBcAMP, the translation pattern became half-way between those of the young and old virgin glands. The anticarcinogenic effect DBcAMP appears to involve a modification of both carcinogen binding to DNA and the gene expression.